Rational design matrix materials for organoid development and application in biomedicine

Organoids are three-dimensional tissue analogues grown in vitro. Although they are not human organs in the strict sense, they can mimic the structure and function of tissues in vivo to the maximum extent, and have broad application prospects in the fields of organ development, personalized medicine, regenerative medicine, disease modeling, drug screening, gene editing, etc. There is even hope that organoids can replace experimental animals for preclinical testing, which will greatly shorten the cycle of preclinical testing and improve its efficiency. Nowadays, Matrigel remains the predominant substitute for organoid culture systems. At the same time, new extracellular matrix or inspired polymer materials with tunable and optimized biochemical and biophysical properties continue to emerge, which are of great significance for efficient and high-level cultivation of organoids. In this review, we critically evaluate how mechanobiological signaling dynamics at the cell-matrix interface inform the rational engineering of biomimetic extracellular matrices to achieve standardized and phenotypically regulated patient-derived organoid cultures. Then, we systematically classify hydrogel-based matrices encompassing natural, biohybrid, synthetic, protein-engineered and DNA crosslinked matrix systems by their biocompatibility and functional compatibility. Focusing on cancer oncogenesis and progression research, drug development and personalized medicine, we highlight biomimetic hydrogel innovations that recapitulate tumor organoids development. By summarizing the obstacles that hinder the development of organoid hydrogels, we hope to provide an outlook on the future directions for the development of organoid hydrogels and promote the application of organoids in the field of biomedicine.